No Clear Evidence Linking Nausea Drug to Serious Birth Defects

Small risk of cardiac defects suggested, but benefits outweigh risks

Ondansetron (Zofran), a drug given to treat severe nausea and vomiting during pregnancy, was not linked to an increased risk of serious birth defects, a small systematic review showed.

The eight examined studies showed conflicting results, but the three largest studies found no increased risk of birth defects associated with ondansetron use, reported Shaun D. Carstairs, MD, of the University of California in San Diego, writing in Obstetrics and Gynecology.

There were two smaller studies that showed a slightly increased risk of cardiac birth defects, although these results were not consistent. A small cohort study of 1,349 neonates found that ondansetron was associated with a "slightly increased" risk of cardiac malformations compared with another drug, meclizine (OR 1.62), with the majority of these being septal defects (17 out of 19, OR 2.05).

The other study was published only in abstract form and presented at a medical conference, examining 1,248 women who had a prescription for ondansetron. In this case, ondansetron use was linked to an increased prevalence of heart defects (OR 2.0). But because the study was in abstract only, questions about its specific study methods exist.

Ondansetron is classified as FDA Pregnancy Category B (where animal studies have failed to show a risk, but there is a lack of well-controlled studies in pregnant women), but recent safety concerns have been raised regarding the link between ondansetron and birth defects -- some encouraging legal action against the makers of the drug.

Carstairs told MedPage Today that the review wanted to address the conflicting data about birth defects that had been reported. He emphasized that ondansetron is not a first-line medication, but in cases where the first-line medication has failed, ondansetron should be an option for providers.

"There has been concern from a medical/legal standpoint, but providers shouldn't be afraid to use this medication when indicated," he said. "It's not clear if there is a link between ondansetron and cardiovascular birth defects, but it's a small risk, and the medication still has benefit."

Patients with inadequately controlled nausea and vomiting in pregnancy may develop hyperemesis gravidarum, which Carstairs writes is a risk that "needs to be weighed against the very small potential risks associated with ondansetron use."

Carstairs said separately that more studies are needed to definitively answer the question about a link between ondansetron and birth defects, but studies have not been conducted in human populations -- likely due to ethical concerns.

"It's tough because of the ethics of including pregnant women in randomized controlled trials, but more data are definitely needed," he said.

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